Circulating Fibroblast Growth Factor-23 Levels are Associated with an Increased Risk of Anemia Development in Patients with Nondialysis Chronic Kidney Disease

Nam, Ki Heon; Kim, Hyoungnae; An, Seokyung; Lee, Misol; Uk, Min; Park, Sun-Hee; Yoo, Tae‐Hyun; Lee, Kyu Beck; Kim, Yeong Hoon; Sung, Su Ah; Lee, Joongyub; Kang, Shin Wook; Choi, Kyu Hun; Ahn, Curie; Han, Seung Hyeok

doi:10.1038/s41598-018-25439-z

Cited by 40 publications

(38 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This finding, which has not been previously reported in CKD stage 1-5 patients, is in accordance with studies in hemodialysis and transplanted patients, in whom the presence of iron deficiency promoted a rise in FGF-23 levels and on the contrary, iron intravenous administration reduced its levels [43,44]. Of note, a recent paper, again in non dialysis CKD patients, found that high serum FGF-23 levels were associated with an increased risk for anemia [45]. Finally, serum levels of 25-OH vitamin D were significantly higher in the group of patients with lower than median cFGF-23 value and also lower than median value of serum phosphate.…”

Section: Cfgf-23 and Sklotho Associations With Cardiovascular Risk Fasupporting

confidence: 91%

Fibroblast Growth factor 23 and α-Klotho protein are associated with adverse clinical outcomes in non dialysis chronic kidney disease stage 1-5 patients

Manou

Thodis

Arsos

et al. 2019

Preprint

View full text Add to dashboard Cite

Background: Fibroblast Growth Factor 23 (FGF-23) and α-Klotho contribute to the patho-genesis of chronic kidney disease - mineral and bone disorders (CKD-MBD). The aim of our study was to evaluate the association of FGF-23 and α-Klotho levels with CKD-MBD parameters, as well as with renal prognosis and mortality, in CKD patients stage 1-5, not in renal replacement therapy (RRT). Methods: 128 patients were included. At enrollment GFR was measured (mGFR) and plasma levels of carboxyl terminal FGF-23 (cFGF-23) and soluble α-Klotho (sKlotho) were determined by ELISA. Abdominal aorta calcification (AAC) score was assessed in lateral abdominal X ray. The composite end point (event) was initiation of RRT or death. Follow-up was five years (median 36, range 2-60 months). Results: mGFR significantly correlated with cFGF-23 and sKlotho negatively and posi-tievely respectively (p<0.0001 for both). Multiple regression analysis showed an inde-pendent correlation of cFGF-23 with mGFR, 25-OH vitamin D, presence of diabetes melli-tus and AAC score, of sKlotho with mGFR and phosphate and of AAC score with sKlotho and cFGF-23. Multivariate regression tree analysis, led to the formation of three regression groups (A, B, C) based on two “cut off” values: mGFR levels of 60.85 ml/min/1.73m2 and serum phosphate levels of 3.7 mg/dl. These groups significantly correlated with the five CKD stages and additionally cFGF-23 and sKlotho plasma levels (p<0.0001 for both). During follow-up, 40 out of the 128 patients, (31.2%) either initiated RRT or died (31 and 9 respectively). Kaplan Meier survival analysis showed that groups of patients with cFGF-23 levels less than median and those with sKlotho more than median value showing a more favorable course, regarding outcome (p=0.0003 for cFGF-23, p=0.004 for s-Klotho). In Cox regression analysis the association of cFGF-23 (p=0.04), sKlotho (p=0.008) and AAC score (p=0.01) with the presence of “event” remained significant after adjustment for traditional and CKD- related covariates. Conclusions: In CKD patients stage 1-5, cFGF-23 and sKlotho levels are associated with adverse clinical outcomes. mGFR and serum phosphate, in association with sKlotho lev-els, may provide a “new classification” of CKD patients, which appears to be predictive of outcome.

show abstract

Section: Cfgf-23 and Sklotho Associations With Cardiovascular Risk Fasupporting

confidence: 91%

Fibroblast Growth factor 23 and α-Klotho protein are associated with adverse clinical outcomes in non dialysis chronic kidney disease stage 1-5 patients

Manou

Thodis

Arsos

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…In CKD patients, associations of FGF23 serum concentrations with hemoglobin levels and the presence of anemia have been described [ 17 , 18 , 19 ]. However, in these studies, only cFGF23 was measured and no analysis of potential underlying mechanisms was undertaken.…”

Section: Introductionmentioning

confidence: 99%

The Role of Iron and Erythropoietin in the Association of Fibroblast Growth Factor 23 with Anemia in Chronic Kidney Disease in Humans

Bielesz

Reiter

Hammerle

et al. 2020

JCM

View full text Add to dashboard Cite

Anemia in chronic kidney disease (CKD) is an almost universal complication of this condition. Fibroblast growth factor 23 (FGF23), a key-player in mineral metabolism, is reportedly associated with anemia and hemoglobin levels in non-dialysis CKD patients. Here, we sought to further characterize this association while taking into account the biologically active, intact fraction of FGF23, iron metabolism, and erythropoietin (EPO). Hemoglobin, EPO, iron, and mineral metabolism parameters, including both intact and c-terminal-FGF23 (iFGF23 and cFGF23, respectively) were measured cross-sectionally in 225 non-dialysis CKD patients (stage 1–5, median eGFR: 30 mL/min./1.73m2) not on erythropoiesis stimulating agents or intravenous iron therapy. Statistical analysis was performed by multiple linear regression. After adjustment for eGFR and other important confounders, only cFGF23 but not iFGF23 was significantly associated with hemoglobin levels and this association was largely accounted for by iron metabolism parameters. cFGF23 but not iFGF23 was also associated with mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV), again in dependence on iron metabolism parameters. Similarly, EPO concentrations were associated with cFGF23 but not iFGF23, but their contribution to the association of cFGF23 with hemoglobin levels was marginal. In pre-dialysis CKD patients, the observed association of FGF23 with hemoglobin seems to be restricted to cFGF23 and largely explained by the iron status.

show abstract

“…In a cross-sectional study of patients representing a spectrum of CKD severity, increased FGF23 levels were significantly associated with deteriorating renal function [ 15 ]. For reasons that are not yet clear, FGF23 also may be related to the development of iron deficiency anemia; in a recent cohort study, elevated concentrations of FGF23 were associated with a higher incidence of anemia, particularly in patients with iron deficiency [ 16 ]. Importantly, increased serum FGF23 concentrations are associated with increased risk of cardiovascular events and death in CKD [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Mechanism of Action and Clinical Attributes of Auryxia® (Ferric Citrate)

Ganz

Bino

Salusky

2019

Drugs

View full text Add to dashboard Cite

Chronic kidney disease (CKD) is a major cause of morbidity and premature mortality and represents a significant global public health issue. Underlying this burden are the many complications of CKD, including mineral and bone disorders, anemia, and accelerated cardiovascular disease. Hyperphosphatemia and elevated levels of fibroblast growth factor 23 (FGF23) have been identified as key independent risk factors for the adverse cardiovascular outcomes that frequently occur in patients with CKD. Auryxia ® (ferric citrate; Keryx Biopharmaceuticals, Inc., Boston, MA, USA) is an iron-based compound with distinctive chemical characteristics and a mechanism of action that render it dually effective as a therapy in patients with CKD; it has been approved as a phosphate binder for the control of serum phosphate levels in adult CKD patients treated with dialysis and as an iron replacement product for the treatment of iron deficiency anemia in adult CKD patients not treated with dialysis. This review focuses on Auryxia, its mechanism of action, and the clinical attributes that differentiate it from other, non-pharmaceutical-grade, commercially available forms of ferric citrate and from other commonly used phosphate binder and iron supplement therapies for patients with CKD. Consistent with the chemistry and mechanism of action of Auryxia, multiple clinical studies have demonstrated its efficacy in both lowering serum phosphate levels and improving iron parameters in patients with CKD. Levels of FGF23 decrease significantly with Auryxia treatment, but the effects associated with the cardiovascular system remain to be evaluated in longer-term studies.

show abstract

Circulating Fibroblast Growth Factor-23 Levels are Associated with an Increased Risk of Anemia Development in Patients with Nondialysis Chronic Kidney Disease

Cited by 40 publications

References 43 publications

Fibroblast Growth factor 23 and α-Klotho protein are associated with adverse clinical outcomes in non dialysis chronic kidney disease stage 1-5 patients

Fibroblast Growth factor 23 and α-Klotho protein are associated with adverse clinical outcomes in non dialysis chronic kidney disease stage 1-5 patients

The Role of Iron and Erythropoietin in the Association of Fibroblast Growth Factor 23 with Anemia in Chronic Kidney Disease in Humans

Mechanism of Action and Clinical Attributes of Auryxia® (Ferric Citrate)

Contact Info

Product

Resources

About